Immediate corticosteroids with rituximab as needed to stop ocular myasthenia from spreading

Immediate Corticosteroid Therapy and Rituximab to Prevent Generalization in Ocular Myasthenia: a PROBE Multicenter Open-label Randomized Controlled Trial.

We will test whether starting corticosteroids right away, and adding rituximab if eye symptoms come back, can prevent recent-onset ocular myasthenia from spreading to other muscles in adults.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 128 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fondation Ophtalmologique Adolphe de Rothschild (Research network)
• Drugs / interventions: rituximab, prednisone
• Locations: 11 sites (Bordeaux and 10 other locations)
• Trial ID: NCT06342544 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open-label, randomized Phase 3 trial comparing immediate corticosteroid therapy (with rituximab added for recurrence) to usual care in adults with ocular-onset myasthenia gravis diagnosed within the past six months. Participants must have eye-limited symptoms for at least one month and be naïve to immunosuppressive therapy. The trial uses a PROBE design across several French university hospitals to measure whether early intervention reduces later generalization to bulbar, axial, or limb muscles. Follow-up focuses on the rate and timing of generalization during the early years when the autoimmune response typically matures.

Who should consider this trial

Good fit: Adults (≥18) with a diagnosis of ocular myasthenia within the past six months, eye-limited symptoms for at least one month, no prior immunosuppressive treatment, and no signs of generalized weakness are ideal candidates.

Not a fit: Patients with thymoma, Graves' ophthalmopathy or other non-ocular causes of eye movement problems, symptom onset more than one year earlier, or existing generalized myasthenia are unlikely to benefit from this preventive approach.

Why it matters

Potential benefit: If successful, this approach could lower the chance that eye-only myasthenia spreads to other muscles, reducing the risk of respiratory complications and the need for long-term immunosuppression.

How similar studies have performed: Some retrospective and observational data suggest early corticosteroids can reduce generalization and rituximab is effective in generalized myasthenia, but a randomized trial combining immediate steroids with rituximab as needed for preventing generalization is novel and not yet validated.

Eligibility criteria

Inclusion Criteria:

* Patients over 18 years of age
* Diagnosis of ocular myasthenia within the last 6 months, defined :

  * either by a typical clinical examination objectified by an expert clinician: ptosis and/or binocular diplopia, with a variable and fluctuating character (either spontaneous or provoked by effort or rest)
  * or by positive anti-AChR antibodies or the presence of decrement on repetitive nerve stimulation or a positive edrophonium test
* Ocular symptoms lasting at least one month and limited to extra-ocular muscles (weakness in one or both orbicularis oculi)
* No non-ocular symptoms on MMS, MGC and MG-ADL.
* Naïve to immunosuppressive therapy for ocular myasthenia gravis.

Exclusion Criteria:

* Thymoma
* Pupillary anomaly other than that resulting from previous local disease or surgery.
* Signs of restrictive abduction or supraduction myopathy due to dysthyroid ophthalmopathy.
* Graves' ophthalmopathy
* Onset of ocular symptoms more than one year before screening date
* Hypersensitivity to rituximab, murine proteins, prednisone, methylprednisone, aziathioprine or 6-mercaptopurine, paracetamol, dexchlorpheniramine.
* Any infectious condition
* Patients with severe immune deficiency
* Severe heart failure (New York Heart Association (NYHA) Class IV) or severe uncontrolled heart disease
* Severe hepatic insufficiency
* Psychotic states not yet controlled by treatment
* Hyperuricemia on xanthine oxidase inhibitors (allopurinol and febuxostat)
* Risk of angle-closure glaucoma
* Risk of urinary retention due to urethro-prostatic disorders
* Vaccination with live attenuated vaccine required during study and up to 6 months after rituximab discontinuation
* Women of childbearing age who do not wish to use effective contraception during their participation and at least 12 months after
* Pregnant or breast-feeding women

Where this trial is running

Bordeaux and 10 other locations

• Centre Hospitalier Universitaire De Bordeaux — Bordeaux, France (Recruiting)
• Hôpital Raymond Pointcarre — Garches, France (Not_yet_recruiting)
• Centre Hospitalier Universitaire De Lille — Lille, France (Recruiting)
• Hospices Civils De Lyon — Lyon, France (Recruiting)
• Centre Hospitalier Universitaire De Nice — Nice, France (Recruiting)
• Chno — Paris, France (Active_not_recruiting)
• Hôpital de la Pitié-Salpêtrière — Paris, France (Not_yet_recruiting)
• Centre Hospitalier Sainte Anne — Paris, France (Active_not_recruiting)
• Fondation Adolphe de Rothschild — Paris, France (Recruiting)
• Les Hopitaux Universitaires De Strasbourg — Strasbourg, France (Recruiting)
• Centre Hospitalier Universitaire De Toulouse — Toulouse, France (Active_not_recruiting)

Study contacts

• Study coordinator: Antoine Gueguen

Conditions Ocular Myasthenia Gravis